1. Field of the Invention
The present invention relates to novel aspartylamide derivatives and salts thereof as well as a sweetener containing the same as an active ingredient.
2. Discussion of the Art
In recent years, eating habits have been improved to a high level, and fatness caused by excessive intake of sugar and diseases accompanied by the fatness have been at issue. Therefore, the development of a low-calory sweetener that replaces sugar has been in demand. As a sweetener that has been widely used at present, there is aspartame which is excellent terms of a safety and sweetness properties. However, it involves a problem of a stability. In order to improve the stability and the sweetness intensity, an aspartylamide derivative which is a condensate of aspartic acid and .beta.-amino-alcohol and which is free from an ester linkage was studied. Thus, the compounds described in U.S. Pat. No. 4,423,029, European Patent No. EP 0203540A, J. Med. Chem., 13, 1217 (1970) or Tetrahedron Letters, 35, 6891 (1994) were found. Meanwhile, it is described in French Patent No. 2,697,844 that aspartyldipeptide derivatives in which an alkyl group has been introduced into an amino group exhibits an extremely increased degree of sweetness. However, these compounds do not satisfy the stability.
Problems To Be Solved by the Invention
The present invention is to provide novel aspartylamide derivatives and salts thereof which are obtained by using an easily-obtainable amino-alcohol component and which exhibit a high level of safety and an excellent stability, as well as a low-calory sweetener containing the same as an active ingredient.
Means Taken For Solving the Problems
In order to solve the above-mentioned problems, the present inventors have assiduously conducted investigations with respect to an N-alkyl group and an amino-alcohol component of aspartylamide derivatives, and have consequently found that aspartylamide derivatives represented by the following formula (I) are used as a sweetener which is excellent in terms of sweetness intensity, stability and sweetness properties. This finding has led to the completion of the present invention. EQU R.sub.1 --NHC--H(CH.sub.2 COOH)CONH--C.sup.2 R.sub.2 R.sub.3 --C.sup.3 H(OH)--R.sub.4 (I)
wherein
R.sub.1 represents H, or a saturated, unsaturated, acyclic, and/or cyclic hydrocarbon group having from 1 to 13 carbon atoms; PA1 R.sub.2 and R.sub.3 each represent H, or a substituent selected from an alkyl group having from 1 to 6 carbon atoms, an alkoxyalkyl group having from 2 to 7 carbon atoms, a hydroxyalkyl group having from 2 to 7 carbon atoms, a phenyl group, and a 2-furyl group, or R.sub.2 and R.sub.3 taken together with the carbon to which they are attached form a cycloalkyl group containing 3 to 6 carbon atoms; PA1 when R.sub.1 is a saturated, unsaturated, acyclic, and/or cyclic hydrocarbon group having from 1 to 13 carbon atoms, R.sub.4 represents an alkyl group having from 1 to 12 carbon atoms, or a substituent represented by formula (II) or (III), and when R.sub.1 is H, R.sub.4 represents a substituent represented by formula (III) EQU --(CHR.sub.5).sub.n --R.sub.6 (II) EQU --(CH.sub.2).sub.m C.sup.4 HR.sub.7 R.sub.6 (III) PA1 R.sub.5 represents H, or an alkyl group having from 1 to 4 carbon atoms, PA1 R.sub.6 represents a cyclic group containing up to 10 ring carbon atoms and up to 12 total carbon atoms, which cyclic group is cycloalkyl, cycloalkenyl, lower alkyl substituted cycloalkyl or cycloalkenyl, bicycloalkyl, bicycloalkenyl, or tricycloalkyl, and PA1 n represents 0 or 1, and PA1 in formula (III) PA1 R.sub.7 and R.sub.8 each represent H; a cycloalkyl group having from 3 to 4 carbon atoms; an alkyl group having from 1 to 6 carbon atoms; an alkoxyalkyl group having from 2 to 7 carbon atoms; a phenyl group; a phenyl group having a substituent selected from F, Cl, Br, I, a hydroxy group, an alkyl group having from 1 to 6 carbon atoms, an alkoxy group having from 2 to 7 carbon atoms, a cyano group, a nitro group, an acetyl group, an amino group and an acetylamino group in the 2-, 3- or 4-position; a phenyl group having a methylenedioxy group, a trimethylene group or a tetramethylene group in the 2- and 3-positions or in the 3- and 4-positions; a 2-, 3- or 4-pyridyl group; a 2- or 3-furyl group; or a 2- or 3-thienyl group, and PA1 m represents 0 or 1; and the C.sup.1 -configuration is (S), and the C.sup.2 -, C.sup.3 - and C.sup.4 -configurations are (R), (S) or (RS).
in which
in formula (II)